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Global Translational Medicine Inflammatory gene-environment interactions in COPD

IL13, and CSF2 genes . Numerous reports associated IL4 We also analyzed the С5 (rs17611) polymorphism
[16]
gene polymorphisms with allergic rhinitis , bronchial which are missense variant according to functional
[39]
asthma , and COPD [41,42] . IL4 is produced by activated analysis in SNPinfo Web Server (https://snpinfo/niehs.
[40]
immune cells and binds to the IL4 receptor . The human nih.gov). C5 gene is located at chromosome 9q33.2.
[16]
IL4R (IL4RA) is located at chromosome 16p12.1 and Significant association with COPD was observed only
encodes the alpha chain of the IL4 receptor . Analysis for G allele of C5 (rs17611) as part of informative
[43]
of gene-gene interaction of inflammatory genes loci to protective gene-gene combinations in smokers together
COPD risk showed that A allele of IL4RA (rs1805010) was with A allele of IL19 (rs2243193), T allele of IL12A
a part of two informative combinations associated with (rs2243115), and T allele of PPBC (rs352010). C5
COPD risk in non-smokers. These combinations included plays an important role in the inflammatory response,
functionally related cytokine genes IL12RB2 (rs3762317), host homeostasis, and host defense [25] . Effects of C5
IL12A (rs2243115), IL4 (rs2070874), and IL24 (rs291107). gene polymorphisms, including rs17611, have been
We detected significant association of IL4RA (rs1805010) extensively investigated in cardiovascular disease [49] ,
to the respiratory variables in COPD patients; the FVC artery atherosclerosis [50] , bacterial meningitis [51] , and
level was significantly lower in homozygous carriers of the rheumatoid arthritis [52] .
more frequent A allele of the IL4RA (rs1805010) locus and
heterozygous carriers had higher FEV1 level. There are several limitations in this study. The sample
size of this study is limited and restricted to Tatar
We also analyzed the FASLG (rs763110) and FAS population from Russia. We will further expand the sample
(rs1800682) polymorphisms. Significantly low level size to verify the results of this study. The strength of this
of pulmonary function was detected in carriers of study is the careful selection of the gene panel based on
AA genotype of FAS (rs1800682) (for FVC) and TT hypothesized biological pathways.
genotype of FASLG (rs763110) (for FVC and FEV1).
Moreover, the smoking index was significantly increased 5. Conclusion
in carriers of CC genotype of FASLG (rs763110). FAS
(rs1800682) A allele and AA genotype were associated The single locus and multilocus analysis showed distinctive
with COPD risk in smokers only in combination with patterns of association of inflammatory genes loci with
IL12A (rs2243115) and PPBP (rs352010) genes. Allele COPD in groups stratified by smoking status. To the best
C of FASLG (rs763110) was a part of two informative of our knowledge, this is the first study portraying the
combinations associated with low COPD risk in smokers contribution of IL19 (rs2243193), IL24 (rs291107), and
and non-smokers. FAS is a member of the tumor necrosis PPBP (rs352010) polymorphisms to COPD. Our study
factor receptor superfamily and plays a central role in provides new insights into the interactions between the
regulation of programmed cell death . The FAS gene is inflammatory genes and the environmental factors of
[21]
located at chromosome 10q23.31 and widely expressed COPD in the Tatar population from Russia.
in in most tissues, including lung . FASLG is a member Acknowledgments
[44]
of the tumor necrosis factor superfamily . The FASLG
[21]
gene is located at chromosome 1q24.3 and expressed in We are grateful to all COPD patients and healthy volunteers
activated immune cells . Several functional SNPs of FAS for their participation in this study. We also thank the
[44]
and FASLG genes were associated with susceptibility to clinicians and hospital staff (Ufa City Hospitals No. 21,
non-small cell lung cancer . Ufa, Russia) who assisted with sample and data collection
[45]
The TGFb1 gene is located at chromosome 19q13.2 for this study.
and encodes a secreted ligand of the TGF-β superfamily Funding
of proteins . TGFb1 is highly expressed in patients with
[23]
COPD, asthma, and lung fibrosis . Published meta- DNA samples for the study are taken from “Collections
[46]
analyses failed to support the association of TGFb1 gene of human biological materials IBG UFIC RAS” supported
loci with COPD, and demonstrated a race-specific and by the Federal Agency for Scientific Organizations
stage-dependent association between TGFb1 loci and program for support the bioresource collections
COPD [47,48] . We did not associate TGFb1 (rs1800469) with (No. 007-030164 / 2). The work was performed
COPD in smokers and non-smokers. At the same time, using the equipment of the Centre for Collective Use
the C allele of TGFb1 (rs1800469) was a part of significant “Biomika” and the unique KODINK research facility
protective gene-gene combination associated with a low (Institute of Biochemistry and Genetics, Ufa Federal
risk of COPD in smokers. Moreover, TGFb1 (rs1800469) Research Centre, Russian Academy of Sciences). Partial
was associated with smoking index. financial support for research by the Ministry of Higher

Volume 1 Issue 1 (2022) 11 https://doi.org/10.36922/gtm.v1i1.91